a review of medicinal uses, phytochemistry and biological ......literature on botany, medicinal...

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A review of medicinal uses, phytochemistry and biological activities of Boscia angustifolia Alfred Maroyi Department of Biodiversity, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa. Abstract Boscia angustifolia is an evergreen shrub or small tree widely used as herbal medicine in the Sahel and sub-Saharan Africa. The current study critically reviewed the botany, medicinal uses, phytochemistry and biological activities of B. angustifolia. Literature on botany, medicinal uses, phytochemical and biological activities of B. angustifolia was collected from multiple internet sources including Elsevier, Google Scholar, SciFinder, Web of Science, Pubmed, BMC, Science Direct and Scopus. Complementary information was gathered from pre-electronic sources such as books, book chapters, theses, scientific reports and journal articles obtained from the University library. This study revealed that the species is used as cholagogue and purgative, and herbal medicine for bruises, sores and wounds, gastro-intestinal problems, eye problems and otitis, fever and typhoid fever, gonorrhoea and venereal diseases, malaria, respiratory infections, skin problems, swellings and swollen feet, ulcers and ethnoveterinary medicine. Ethnopharmacological research identified alkaloids, amino acid derivatives, carboxylic acids and their derivatives, saponins, sugars and their derivatives from the bark, fruits, leaves and roots of B. angustifolia. The crude extracts of the species and the compound 7,4'-dimethoxy quercetin isolated from the species exhibited antibacterial, antimycobacterial, antifungal, antiviral, antioxidant, antiplasmodial, antitrypanosomal, GABA A benzodiazepine receptor binding, larvicidal and cytotoxicity activities. Boscia angustifolia should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological activities. Keywords: Boscia angustifolia, Capparaceae, herbal medicine, indigenous knowledge, Sahel, sub-Saharan Africa INTRODUCTION Boscia angustifolia A. Rich. is an evergreen shrub or small tree belonging to the Capparaceae or Capparidaceae or caper family. The Capparaceae family contains 33 genera and approximately 700 species distributed in tropical and subtropical regions of the world. 1-3 Boscia Lam. is a genus of shrubs or small trees consisting of 37 species, mostly in tropical and southern Africa, a few in Madagascar, one confined to Arabia, mostly in semi-arid or seasonally dry areas. 2,4,5 Several Boscia species are used as herbal medicines in tropical Africa and these include B. albitrunca (Burch.) Gilg & Gilg-Ben., B. angustifolia, B. coriacea Graells, B. foetida Schinz, B. longifolia Hadj- Moust., B. madagascariensis (DC.) Hadj-Moust., B. mossambicensis Klotzsch., B. salicifolia Oliv. and B. senegalensis Lam. 6-8 Iwu 6 argued that the medicinal properties of Boscia species could be attributed to alkaloids, flavonoids, sesquiterpenes and their glycosides, sulphur compounds and lipids that are associated with the genus. Boscia angustifolia is categorized as a multipurpose species in Burkina Faso, Ethiopia, Eritrea and Tanzania, used as a source of charcoal, cosmetics, dye or tannin, fodder, food, firewood, construction materials, ethnoveterinary medicines, herbal medicines, shade, fodder, source of bee forage, toothbrush, reclaiming degraded sites and source of timber for furniture and carvings. 9-27 The fruits of B. angustifolia are edible but bitter, however, seeds are cooked and then eaten. 28 The powdered seeds are mixed with millet (Eleusine coracana Gaertn.) flour and added to soups or cereals. 28 Boiled pieces of wood have been used to sweeten milk 7 and the bark of B. angustifolia has been used as tea in Kenya. 29 Boscia angustifolia appears to be an important source of herbal medicine within its distributional range in the Sahel and sub-Saharan Africa, and therefore, there is need for formal documentation and systematic research which is beneficial to indigenous and traditional systems of herbal medicine. 30,31 It is within this context that this review was undertaken aimed at reviewing the botany, medicinal uses and biological activities of B. angustifolia so as to provide baseline data required in evaluating the therapeutic potential of the species. Botanical profile of Boscia angustifolia The genus name Boscia is in honour of a French naturalist, botanist, zoologist and horticulturist Louis Auguste Guillaume Bosc (1759-1828). 32 The species name angustifolia” means “narrow-leaved” in reference to narrow oblong and sometimes wider leaves. 4,33 Two infraspecies of B. angustifolia are recognized, namely B. angustifolia var. angustifolia with glabrous leaves occurring from Senegal to Somalia, Kenya and northern Tanzania and var. corymbosa (Gilg) DeWolf with short and hairy leaves below and occurring from Uganda and Kenya southward to northern South Africa. 7,34-40 However, most ethnobotanical and ethnopharmacological literature do not separate B. angustifolia into specific varieties, but rather to B. angustifolia sensu lato, and this is the approach that has been adopted in this study. Boscia angustifolia is commonly referred to as “rough- leaved shepherd tree” in English. Synonyms associated with B. angustifolia include B. caloneura Gilg, B. corymbosa Gilg, B. dawei Sprague & M.L. Green, B. engleri Gilg & Gilg-Ben., B. fischeri Pax, B. homblei De Wild., B. patens Sprague & M.L. Green, B. reticulata Hochst. ex A. Rich. and Boscia senegalensis Hochst. ex Walp. 34-37,39,40 Boscia angustifolia is an evergreen shrub or Alfred Maroyi /J. Pharm. Sci. & Res. Vol. 11(10), 2019, 3420-3428 3420

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Page 1: A review of medicinal uses, phytochemistry and biological ......Literature on botany, medicinal uses, phytochemical and biological activities of angustifolia was collected from multiple

A review of medicinal uses, phytochemistry and biological activities of Boscia angustifolia

Alfred Maroyi Department of Biodiversity, University of Limpopo, Private Bag X1106, Sovenga 0727, South Africa.

Abstract Boscia angustifolia is an evergreen shrub or small tree widely used as herbal medicine in the Sahel and sub-Saharan Africa. The current study critically reviewed the botany, medicinal uses, phytochemistry and biological activities of B. angustifolia. Literature on botany, medicinal uses, phytochemical and biological activities of B. angustifolia was collected from multiple internet sources including Elsevier, Google Scholar, SciFinder, Web of Science, Pubmed, BMC, Science Direct and Scopus. Complementary information was gathered from pre-electronic sources such as books, book chapters, theses, scientific reports and journal articles obtained from the University library. This study revealed that the species is used as cholagogue and purgative, and herbal medicine for bruises, sores and wounds, gastro-intestinal problems, eye problems and otitis, fever and typhoid fever, gonorrhoea and venereal diseases, malaria, respiratory infections, skin problems, swellings and swollen feet, ulcers and ethnoveterinary medicine. Ethnopharmacological research identified alkaloids, amino acid derivatives, carboxylic acids and their derivatives, saponins, sugars and their derivatives from the bark, fruits, leaves and roots of B. angustifolia. The crude extracts of the species and the compound 7,4'-dimethoxy quercetin isolated from the species exhibited antibacterial, antimycobacterial, antifungal, antiviral, antioxidant, antiplasmodial, antitrypanosomal, GABAA–benzodiazepine receptor binding, larvicidal and cytotoxicity activities. Boscia angustifolia should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological activities.

Keywords: Boscia angustifolia, Capparaceae, herbal medicine, indigenous knowledge, Sahel, sub-Saharan Africa

INTRODUCTION Boscia angustifolia A. Rich. is an evergreen shrub or small tree belonging to the Capparaceae or Capparidaceae or caper family. The Capparaceae family contains 33 genera and approximately 700 species distributed in tropical and subtropical regions of the world.1-3 Boscia Lam. is a genus of shrubs or small trees consisting of 37 species, mostly in tropical and southern Africa, a few in Madagascar, one confined to Arabia, mostly in semi-arid or seasonally dry areas.2,4,5 Several Boscia species are used as herbal medicines in tropical Africa and these include B. albitrunca (Burch.) Gilg & Gilg-Ben., B. angustifolia, B. coriacea Graells, B. foetida Schinz, B. longifolia Hadj-Moust., B. madagascariensis (DC.) Hadj-Moust., B. mossambicensis Klotzsch., B. salicifolia Oliv. and B. senegalensis Lam.6-8 Iwu6 argued that the medicinal properties of Boscia species could be attributed to alkaloids, flavonoids, sesquiterpenes and their glycosides, sulphur compounds and lipids that are associated with the genus. Boscia angustifolia is categorized as a multipurpose species in Burkina Faso, Ethiopia, Eritrea and Tanzania, used as a source of charcoal, cosmetics, dye or tannin, fodder, food, firewood, construction materials, ethnoveterinary medicines, herbal medicines, shade, fodder, source of bee forage, toothbrush, reclaiming degraded sites and source of timber for furniture and carvings.9-27 The fruits of B. angustifolia are edible but bitter, however, seeds are cooked and then eaten.28 The powdered seeds are mixed with millet (Eleusine coracana Gaertn.) flour and added to soups or cereals.28 Boiled pieces of wood have been used to sweeten milk7 and the bark of B. angustifolia has been used as tea in Kenya.29 Boscia angustifolia appears to be an important source of herbal medicine within its distributional range in the Sahel

and sub-Saharan Africa, and therefore, there is need for formal documentation and systematic research which is beneficial to indigenous and traditional systems of herbal medicine.30,31 It is within this context that this review was undertaken aimed at reviewing the botany, medicinal uses and biological activities of B. angustifolia so as to provide baseline data required in evaluating the therapeutic potential of the species.

Botanical profile of Boscia angustifolia The genus name Boscia is in honour of a French naturalist, botanist, zoologist and horticulturist Louis Auguste Guillaume Bosc (1759-1828).32 The species name “angustifolia” means “narrow-leaved” in reference to narrow oblong and sometimes wider leaves.4,33 Two infraspecies of B. angustifolia are recognized, namely B. angustifolia var. angustifolia with glabrous leaves occurring from Senegal to Somalia, Kenya and northern Tanzania and var. corymbosa (Gilg) DeWolf with short and hairy leaves below and occurring from Uganda and Kenya southward to northern South Africa.7,34-40 However, most ethnobotanical and ethnopharmacological literature do not separate B. angustifolia into specific varieties, but rather to B. angustifolia sensu lato, and this is the approach that has been adopted in this study.

Boscia angustifolia is commonly referred to as “rough-leaved shepherd tree” in English. Synonyms associated with B. angustifolia include B. caloneura Gilg, B. corymbosa Gilg, B. dawei Sprague & M.L. Green, B. engleri Gilg & Gilg-Ben., B. fischeri Pax, B. homblei De Wild., B. patens Sprague & M.L. Green, B. reticulata Hochst. ex A. Rich. and Boscia senegalensis Hochst. ex Walp.34-37,39,40 Boscia angustifolia is an evergreen shrub or

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small tree with rigid and sometimes spiny branches growing up to 15 m in height.7,38,41 The bole is often deeply and sinuously fluted and twisted with pale grey bark. The leaves are often spirally arranged or occur in groups of two to four on very dwarf spur-branchlets.38 The leaves are elliptic to oblanceolate in shape, leathery, dark green in colour above, much paler and grey-green or bluish green below. The flowers are small, sweet-smelling and yellowish green in colour, occurring in dense clusters on short terminal lateral shoots. The fruit is a berry, which is spherical in shape, hairless and yellowish to almost black in colour with one to two seeds embedded in a sticky pulp.36,38 Boscia angustifolia is widespread, from southern Arabia and Mauritania, Senegal and Gambia eastward to Somalia and southward to northern South Africa.34,35,37,40,43-46 The species has been recorded in dry, open woodland, bushveld, wooded grassland, often on termitaria, also on hills, stony or rocky soils, laterite outcrops and cliffs, loamy soils, and sometimes dry riverbeds at an altitude up to 2000 m above sea level and

in drier regions with rainfall ranging from 200 mm to 800 mm per annum.7,24 Medicinal uses of Boscia angustifolia The bark, bark fibres, fruits, leaves, roots, stem bark and twigs of B. angustifolia are mainly used as cholagogue and purgative, and herbal medicine for bruises, sores and wounds, gastro-intestinal problems, eye problems and otitis, fever and typhoid fever, gonorrhoea and venereal diseases, malaria, respiratory infections, skin problems, swellings and swollen feet, ulcers and ethnoveterinary medicine (Table 1, Figure 1). In Zimbabwe, the roots of B. angustifolia are mixed with roots of Vernonia glabra (Steetz) Vatke as herbal medicine for constipation.47 In Ethiopia, the twigs and roots of B. angustifolia are mixed with those of Capparis tomentosa Lam., Carissa spinarum L., Croton macrostachyus Hochst. ex Delile, Phytolacca dodecandra L'Hér., Ruta chalepensis L., Securidaca longipedunculata Fresen. and Sida schimperiana Hochst. ex A. Rich. and used against evil spirits and evil eye.48-54

Table 1: Medicinal applications of Boscia angustifolia Medicinal use Parts of the plant used Country References Anthelmintic Bark, leaves, roots and stem bark Sudan Elegami et al.55

Bruises, sores and wounds Bark, leaves and roots

Kenya, Mali, Nigeria and Zambia

Keay et al.56; Diallo et al.57; Fowler58; Hassan et al.59; Cheruiyot et al.60; Chalo et al.61

Cholagogue Leaves Mali and Senegal Chini et al.62; Diallo et al.63

Constipation Roots mixed with roots of Vernonia glabra (Steetz) Vatke Zimbabwe Gelfand et al.47

Gastro-intestinal problems (diarrhoea, dysentery and intestinal disorder)

Bark, leaves, roots and stem bark Ethiopia, Kenya, Mali, Nigeria and Tanzania

Gidey et al.27; Keay et al.56; Hassan et al.59; Chalo et al.61; Ahua et al.64; Maregesi et al.65; Omwenga et al.66; Mariita et al.67; Omwenga et al.68

Dislocated backbone Roots Ethiopia Gidey et al.27

Magical purposes (evil spirits and evil eye)

Twigs and roots mixed with Capparis tomentosa Lam., Carissa spinarum L., Croton macrostachyus Hochst. ex Delile, Phytolacca dodecandra L'Hér., Ruta chalepensis L., Securidaca longipedunculata Fresen. and Sida schimperiana Hochst. ex A. Rich.

Ethiopia

Zenebe et al.48; Enyew et al.49; Chekole et al.50; Gidey and Asfaw51; Hishe and Asfaw52; Mekuanent et al.53; Fitsumbirhan et al.54

Eye problems and otitis Bark and leaves Ethiopia and Mali Chini et al.62; Gebrezgabiher et al.69

Fertility Roots Zambia Fowler58

Fever and typhoid fever Bark, leaves, roots and twigs Burkina Faso, Kenya and Nigeria

Keay et al.56; Hassan et al.59; Cheruiyot et al.60; Fowler70

Gonorrhoea and venereal diseases Bark and stem bark Kenya and

Tanzania Maregesi et al.65; Mariita et al.67; Omwenga et al.68

Headache Bark Mali Diallo et al.63; Ahua et al.64 Human immunodeficiency virus (HIV)

Roots Zambia Chinsembu et al.71

Hypertension Stem Nigeria Ajayi et al.72 Insanity Bark and roots Tanzania Mathias73 Joint pains Bark Kenya Chalo et al.61

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Medicinal use Parts of the plant used Country References

Malaria Bark, bark fibres, leaves, stem bark and twigs

Kenya, Mali and Zambia

Fowler70; Koch et al.74; Bizimana et al.75; Kokwaro76; Chinsembu77; Diarra et al.78; Muthaura et al.79

Neuralgia Bark Mali Chini et al.62 Pain Leaves Mali Danton et al.80 Pesticide Leaves and stems Kenya Menge et al.81; Karani et al.82

Purgative Bark, fruits, leaves, roots and stem bark Mali and Sudan Elegami et al.55; Chini et al.62

Respiratory infections (chest pains, cough, pneumonia, throat infection and tuberculosis)

Bark, leaves and roots Ethiopia, Kenya, Nigeria and Tanzania

Keay et al.56; Hassan et al.59; Cheruiyot et al.60; Mariita et al.67; Otieno et al.83; Legesse84

Retained after birth Leaves and stems Kenya Kaingu et al.85 Snake bite Roots and stem bark Eritrea Kaushik et al.86 Skin problems (boils and mumps) Leaves, roots and stem bark Nigeria and

Tanzania Keay et al.56; Hassan et al.59; Maregesi et al.65

Swellings and Swollen feet Bark

Ethiopia, Kenya, Senegal and Sudan

Chalo et al.61; Diallo et al.63; Doka and Yagi87; Tefera and Kim88

Ulcers (gastric and genital) Roots Namibia and

Zambia Chinsembu et al.71; Chinsembu et al.89

Urinary infections Leaves and roots Nigeria Keay et al.56; Hassan et al.59

Vomiting Bark, leaves and stems Kenya Kaingu et al.85; Tsigemelak et al.90

Weight loss Leaves Burkina Faso Pare et al.91 Ethnoveterinary medicine (ectoparasites, fever, gynaecological problems and wounds)

Bark, leaves and roots Eritrea, Ethiopia, Kenya and Uganda

Bein et al.14; Zorloni23; Mekuanent et al.52; Gebrezgabiher et al.69; Byaruhanga et al.92; Kigen et al.93

Figure 1. Medicinal applications of Boscia angustifolia derived from literature records

0 1 2 3 4 5 6 7 8 9 10

CholagogueEye problems and otitis

PurgativeUlcers

Gonorrhoea and venereal diseasesSkin problems

Fever and typhoid feverMalaria

Swellings and swollen feetBruises, sores and woundsEthnoveterinary medicine

Respiratory infectionsGastro-intestinal problems

Literature records No. of countries

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Phytochemical and nutritional composition of Boscia angustifolia Several compounds which include alkaloids, amino acid derivatives, carboxylic acids and their derivatives, saponins, sugars and their derivatives (Table 2) have been

identified from the bark, fruits, leaves and roots of B. angustifolia.7,19,20,59,62,66,67,94,95 Some of the pharmacological activities associated with the species could be attributed to the documented phytochemical compounds.

Table 2: Phytochemical composition of Boscia angustifolia

Phytochemical and nutritional composition Value Plant part Reference 1-Methyl imino thieno [3,4b] naphthalene (%) 10.0 Leaves Salem et al.94 1, 2, 4-Trimethoxy-5,6-dihydrophenanthridin-6-one (%) 2.4 Leaves Salem et al.94 1-H-9-methoxybenz [f] indole (%) 1.9 Leaves Salem et al.94 1,5-Anhydro-d-sorbitol (%) 1.1 Leaves Salem et al.94 2,3,4,5-Tetrahydroxypentanoic acid-1,4-lactone (%) 0.2 Leaves Salem et al.94 2-Deoxy-erythro-pentonic acid (%) 0.3 Leaves Salem et al.94 2-Hydroxy-4-methylpentanoic acid (%) 0.2 Leaves Salem et al.94 4-hydroxystachydrine - Bark and leaves Chini et al.62 4-N,N dimethylaminobutyric acid (%) 0.5 Leaves Salem et al.94 7,4'-dimethoxy quercetin - Leaves Salem et al.94 Acid detergent fibre (g/kg dry matter) 390.3 Leaves Osuga et al.20 Acid detergent lignin (g/kg dry matter) 94.9 Leaves Osuga et al.20 Allofuranose (%) 0.5 Leaves Salem et al.94 Ash (g/100g of dry matter) 8.0 Fruits Lemmens7 Ash (g/kg dry matter) 115.0 Leaves Dereje and Udén19 Calcium (g/kg dry matter) 22.0 Leaves Dereje and Udén19 Carbohydrates (g/100g of dry matter) 78.0 Fruits Lemmens7 Condensed tannins (g/kg dry matter) 22.7 Leaves Dereje and Udén19

Crude protein (g/kg dry matter) 149.4 – 206.0 Leaves Dereje and Udén19;

Osuga et al.20 Dry matter (g/kg dry matter) 405.0 Leaves Dereje and Udén19 Energy (kj/100g) 78.0 Fruits Lemmens7 Erythritol (%) 0.6 Leaves Salem et al.94 Esculetin - Leaves Salem et al.95 Esculetin 6,7 di-methylether - Leaves Salem et al.95 Fat (g/100g of dry matter) 5.0 Fruits Lemmens7 Fibre (g/100g of dry matter) 2.0 Fruits Lemmens7 Fructofuranose (%) 5.8 Leaves Salem et al.94 Glucopyranose (%) 0.3 Leaves Salem et al.94 Glucuronic acid lactone (%) 0.3 Leaves Salem et al.94 Glycerol (%) 2.5 Leaves Salem et al.94 Glycolic acid (%) 0.4 Leaves Salem et al.94 Gulonic acid lactone (%) 0.4 Leaves Salem et al.94 Hexadecanoic acid (%) 0.7 Leaves Salem et al.94 Hydracrylic acid (%) 0.5 Leaves Salem et al.94 in vitro dry matter digestibility (IVDMD) (g/kg dry matter) 0.5 Leaves Dereje and Udén19 Lactic acid (%) 18.1 Leaves Salem et al.94 Lactulose (%) 1.8 Leaves Salem et al.94 Malic acid (%) 1.0 Leaves Salem et al.94 Maltose methyloxime (%) 15.2 Leaves Salem et al.94 Mannitol (%) 1.6 Leaves Salem et al.94 Methyl-3-H pyrrolo [1,2a] indole-9-carboxylate (%) 0.5 Leaves Salem et al.94 Methyl-4-methoxy benzoate - Leaves Salem et al.95 Methyl galactoside (%) 0.3 Leaves Salem et al.94 Methyl leucine (%) 1.5 Leaves Salem et al.94 Methyl mannofuranoside (%) 0.2 Leaves Salem et al.94 Myo-inositol (%) 0.4 Leaves Salem et al.94 Neutral detergent fibre (g/kg dry matter) 570.4 Leaves Osuga et al.20 N, N-dimethyl lysine methyl ester (%) 0.2 Leaves Salem et al.94 Organic matter (g/kg dry matter) 885.0 – Leaves Dereje and Udén19;

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Phytochemical and nutritional composition Value Plant part Reference 919.4 Osuga et al.20

Pentenal (%) 1.0 Leaves Salem et al.94 Phosphorus (g/kg dry matter) 2.4 Leaves Dereje and Udén19 Phthalic acid decyl octyl ester - Leaves Salem et al.95 Proteins (g/100g of dry matter) 7.0 Fruits Lemmens7 Quinic acid (%) 2.5 Leaves Salem et al.94 Rhamnocitrin-4'-O-methylether - Leaves Salem et al.95 Rhamnocitrin-3-O-β-glucopyranoside - Leaves Salem et al.95 Rhamnocitrin-3-O-β-(6"-O-E-p-coumaroyl)-glucopyranoside - Leaves Salem et al.95

Rhamnocitrin-3-O- β-sophoroside - Leaves Salem et al.95 Ribitol (%) 1.1 Leaves Salem et al.94 Ribofuranose (%) 0.8 Leaves Salem et al.94 Ribono-1, 4-lactone (%) 0.5 Leaves Salem et al.94 Soluble tannins (g/kg dry matter) 110.0 Leaves Dereje and Udén19 Sorbose (%) 0.4 Leaves Salem et al.94 Stachydrine - Bark and leaves Chini et al.62 Sucrose (%) 5.2 Leaves Salem et al.94 Talopyranose (%) 1.4 Leaves Salem et al.94 Tamarixetin-7-O-methylether - Leaves Salem et al.95 Tamarixetin-3-O-β-sophoroside-7-O-methylether - Leaves Salem et al.95 Tetrahydroxy-2-furanacetaldehyde (%) 0.8 Leaves Salem et al.94 Threonic acid (%) 0.6 Leaves Salem et al.94 Total extractable phenolics (mg/g dry matter) 13.1 Leaves Osuga et al.20 Total extractable tannins (mg/g dry matter) 1.5 Leaves Osuga et al.20 Trehalose (%) 1.3 Leaves Salem et al.94 Turanose (%) 11.9 Leaves Salem et al.94 Water (g/100g) 81.5 Fruits Lemmens7 Xylose, methyloxime (%) 0.5 Leaves Salem et al.94 Biological activities of Boscia angustifolia The following biological activities have been reported from the bark, inner bark, leaves, roots, stem bark, twig and whole plant part extracts and the compound 7,4'-dimethoxy quercetin isolated from B. angustifolia: antibacterial,55,59,66,67,96,97 antimycobacterial,67 antifungal,67 antiviral,94 antioxidant,94 antiplasmodial,74,79,98,99 antitrypanosomal,75,100 GABAA–benzodiazepine receptor binding,98 larvicidal100 and cytotoxicity94,99,102 activities. Antibacterial activities Elegami et al.55 evaluated antibacterial activities of aqueous, chloroform and methanol whole plant part extracts of B. angustifolia against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa using cup-plate agar diffusion method with ampicillin and neomycin as positive controls. The chloroform and methanol extracts exhibited activities with zone of inhibition ranging from 13 mm to 18 mm which was comparable to 11 mm to 23 mm exhibited by the positive controls.55 Hassan et al.59 evaluated antibacterial activities of aqueous, hexane, petroleum ether and chloroform root extracts of B. angustifolia against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi and Streptococcus pneumoniae using the micro dilution technique with tetracycline (10 mg/ml) as a positive control. The aqueous and chloroform extracts were active against

Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Streptococcus pneumoniae but did not show activity against Salmonella typhi at concentrations ranging from 10 mg/ml to 120 mg/ml with minimum inhibitory concentration (MIC) values ranging from 10.0 mg/ml to 20.0 mg/ml.59. Similarly, Hassan et al.96 evaluated antibacterial activities of chloroform root extracts of B. angustifolia against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi and Streptococcus pneumoniae using the micro dilution technique with tetracycline (10 mg/mL) as a positive control. The extract exhibited activities against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Streptococcus pneumoniae but did not show activity against Salmonella typhi at concentrations of 5 mg/mL to 60 mg/mL with MIC values ranging from 0.6 mg/mL to 1.3 mg/mL.96 Maregesi et al.97 evaluated antibacterial activities of aqueous, n-hexane and methanol stem bark extracts of B. angustifolia against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella typhimurium using a liquid dilution method with ampicillin and rifampicin as positive controls. The n-hexane extract exhibited activities against Bacillus cereus with MIC and minimum bactericidal concentration (MBC) value of 500 µg/mL while MIC value of 1000 µg/mL was exhibited against Staphylococcus aureus.97 Omwenga et al.66 evaluated antibacterial activities of methanol bark

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extracts of B. angustifolia against Staphylococcus aureus, Bacillus subtillis, Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa using disc diffusion and micro titre-dilution techniques with amoxicillin and cefrodoxima as positive controls. The extracts exhibited activities against tested pathogens with zone of inhibition ranging from 7.0 mm to 20.0 mm which was comparable to 17.1 mm to 24.2 mm exhibited by amoxicillin. The MIC value against the tested pathogens was 3.8 mg/50μl while the MBC values ranged from 3.8 mg/50μl to 7.5 mg/50μl.66. Mariita et al.67 evaluated antibacterial activities of methanolic bark extracts of B. angustifolia against Salmonella typhi, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae using the agar disc diffusion method with amoxicillin and ciprofloxacin as positive controls. The extract exhibited activities against tested pathogens with zone of inhibition ranging from 6.7 mm to 9.0 mm which was lower than 13.0 mm to 21.3 mm exhibited by the positive controls. The MIC and MBC values exhibited against Staphylococcus aureus were 37.5 mg/mL and 75.0 mg/mL, respectively.67 Antimycobacterial activities Mariita et al.67 evaluated antimycobacterial activities of methanolic bark extracts of B. angustifolia against Mycobacterium tuberculosis, Mycobacterium Kansasii, Mycobacterium fortuitum and Mycobacterium smegmatis using the BACTEC MGIT 960 system with isoniazid as a positive control. At the highest concentration of 2.0 mg/mL, the extract exhibited activities against tested pathogens.67 Antifungal activities Mariita et al.67 evaluated antifungal activities of methanolic bark extracts of B. angustifolia against Candida albicans, using the agar disc diffusion method with fluconazole as a positive control. The extract exhibited activities against the tested pathogen with zone of inhibition of 6.0 mm which was lower than 13.0 mm exhibited by the positive control.67 Antiviral activities Salem et al.94 evaluated the antiviral activities of aqueous methanol leaf extracts of B. angustifolia and the compound 7,4'-dimethoxy quercetin isolated from the species against avian influenza virus (H5N1) using plaque reduction assay. Both the extract and the compound 7,4'-dimethoxy quercetin exhibited activities with a potential activity against H5N1 infection up to 63 and 68.5%, respectively, at concentration of 80 μg/μl.94 Antioxidant activities Salem et al.94 evaluated the antioxidant activities of aqueous methanol leaf extracts of B. angustifolia and the compound 7,4'-dimethoxy quercetin isolated from the species using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay with ascorbic acid as a positive control. Both the extract and the compound 7,4'-dimethoxy quercetin exhibited activities with half

maximal inhibitory concentration (IC50) values of 41.2 μg/ml and 16.5 μg/ml, respectively which were higher that IC50 value of 1.9 μg/ml exhibited by the positive control, ascorbic acid.94 Antiplasmodial activities Koch et al.74 evaluated antiplasmodial activities of chloroform inner bark extracts of B. angustifolia against a chloroquine-sensitive (D6) strain of Plasmodium falciparum using a semiautomated microdilution technique. The extract showed activity with an IC50 value of >10.0 μg/ml.74 Bah et al.98 evaluated the antiplasmodial activities of dichloromethane and methanol bark and leaf extracts of B. angustifolia against the chloroquine sensitive strain of Plasmodium falciparum (3D7) using the parasite lactate dehydrogenase (pLDH) assay. The methanol leaf extract exhibited moderate activities with IC50 value of 37.6 μg/ml.98 Muthaura et al.79 and Muthaura et al.99 evaluated antiplasmodial activities of aqueous and methanol stem bark extracts of B. angustifolia against chloroquine sensitive (D6) and resistant (W2) Plasmodium falciparum using the semi-automated micro-dilution technique that measures the ability of the extracts to inhibit the incorporation of (G-3H) hypoxanthine into the malaria parasite. The aqueous and methanol extracts exhibited activities with IC50 values of 1.4 μg/ml and 7.4 μg/ml, respectively against D6, and 4.7 μg/ml and 35.9 μg/ml, respectively against W2.79,99 Muthaura et al.99 evaluated the in vivo antimalarial activities of aqueous and methanol stem bark extracts of B. angustifolia by using chloroquine sensitive Plasmodium berghei strain ANKA based on four-day suppressive test. The methanol extract was active in interperitonial injection treatment with chemo-suppression of 60.1% which was lower than 99.9% chemo-suppression of malaria parasites exhibited by the positive control, chloroquine.99 Antitrypanosomal activities Bizimana et al.75 evaluated the antitrypanosomal activities of water, methanol and dichloromethane leaf and twig extracts of B. angustifolia using the low inoculation long Incubation test (LILIT) with diminazene aceturate as a positive control. All the extracts exhibited activities with MIC value of 10.0 μg/ml while diminazene aceturate exhibited MIC value of 0.05 μg/ml.75 Aderbauer et al.100 evaluated antitrypanosomal activities of dichloromethane stem bark extracts of B. angustifolia using the long-term viability assay on Trypanosoma brucei brucei. The extracts exhibited activities with minimum toxic concentration (MTC) and MIC values of 100.0 μg/ml and 200.0 μg/ml, respectively.100 GABAA–benzodiazepine receptor binding activities Bah et al.98 evaluated the GABAA–benzodiazepine receptor binding activities of dichloromethane and methanol bark and leaf extracts of B. angustifolia using the GABAA–benzodiazepine receptor binding assay. A weak GABAA-receptor complex binding activity was exhibited by dichloromethane leaf extract.98

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Larvicidal activities Cepleanu et al.101 evaluated larvicidal activities of aqueous, dichloromethane and methanol root bark and stem bark extracts of B. angustifolia by assessing the effect of extracts at a concentration of 500 mg/ml on mortality of 2nd instar larvae of Aedes aegypti with diazinon as a positive control. Only dichloromethane root bark extract exhibited weak activities with LC100 value after 24 hours of 250.0 μg/ml which was higher than LC100 value of 0.1 μg/ml exhibited by the positive control.101 Cytotoxicity activities Hassan et al.102 evaluated the toxicological effects of the alkaloid and aqueous ethanol root extracts of B. angustifolia on biochemical indices of kidney and liver functions in Wister albino rats. The renal and liver indices were significantly altered at higher doses of alkaloidal extract at 703.6 mg/kg and 1125.7 mg/kg, and aqueous methanol extract at 839.3 mg/kg and 1342.8 mg/kg body weight. The extracts produced histopathological lesions of the liver and kidney such as perivascular cuffs, protein cast, infiltration, slight infiltration at higher doses. There was a significant dose dependent decrease in weight in the rats given higher doses of the extract.102 Muthaura et al.99 evaluated the cytotoxicity activities of aqueous and methanol stem bark extracts of B. angustifolia on Vero cells using the plaque reduction assay. The methanol and water extracts were non-toxic with CC50 value of 1000.0 µg/mL and 6720.0 µg/mL, respectively.99 Salem et al.94 evaluated cytotoxicity activities of aqueous methanol leaf extracts of B. angustifolia and the compound 7,4'-dimethoxy quercetin isolated from the species using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Both the extract and the compound 7,4'-dimethoxy quercetin exhibited activities with TC50 values of 151.0 μg/μl and 81.0 μg/μl, respectively.94

CONCLUSION The present review summarizes the botany, medicinal uses, phytochemistry and pharmacological properties B. angustifolia. Based on presented information, there is not yet enough data correlating the ethnomedicinal uses of the species with its phytochemical and pharmacological properties. Detailed studies on the pharmacokinetics, in vivo and clinical research involving both extracts and compounds isolated from the species are required. Therefore, future research should focus on the molecular modes or mechanisms of action, pharmacokinetics and physiological pathways for specific extracts of the species including identification of the bioactive compounds of the species and their associated pharmacological activities. Conflict of interest The author declares that there is no conflict of interest regarding the publication of this paper. Figure legend Figure 1. Medicinal applications of Boscia angustifolia derived from literature records

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